In the Functional Genomics &Virology Core, we have brought together a diverse group of NIH-funded investigators from basic science and clinical medicine. These investigators have a common interest in using state-of-the-art technologies to better understand the molecular mechanisms underlying the progression from HCV infection to end-stage liver disease. The Center has made great strides in defining global gene expression signatures associated with HCV infection, including the identification of gene expression patterns specifically associated with fibrosis progression. While the Center continues to exploit recurrent HCV after liver transplantation as an investigative tool, we now include a greater emphasis on AIDS, including HCV/HIV-1 co-infection and in vitro HIV infection systems. We have also initiated collaborations with Evergreen Treatment Services to investigate the impact of intravenous drug abuse on HCV-associated liver disease and treatment. The Specific Aims of this Core are to: 1) Supply biological samples, including clinical, in vitro and animal model systems, for microarray, proteomic, and molecular virological analysis. Support services will include sample preparation, RNA and protein isolation, and preparation of materials for genomic and proteomic analyses. Model systems for HCV infection will include, but not be limited to, the SCIDbeige/ Alb-uPA mouse model and the HCV 2a in vitro infection system. AIDS-related studies will include the analysis of liver biopsies from patients co-infected with HCV and HIV-1 and from in vitro HIV-1 infection and in vivo SIV infection systems. 2) Use oligonucleotide microarrays, proteomics, laser/confocal microscopy, and molecular virology to profile the cellular events that occur during HCV-infection, HCV/HIV-1 co-infection, and liver disease and AIDS progression. The overall goal of this Core is to have an integrated systems biology approach to understand the host response to virus infection utlizing genomics tools and classical virological and histological assays. Our ability to integrate gene expression data (this Core) with proteomic data (Proteomics Core) and sophisticated bioinformatic techniques (Bioinformatics &Biostatistics Core) will provide insight into the molecular mechanisms associated with liver disease and AIDS. Ultimately, this will improve patient care by yielding improved diagnostic methods, markers of disease progression, and novel approaches for therapeutic intervention.